Table 2.

Methods and results of longitudinal follow-up studies.

Authors	MS sample size at follow-up	Healthy controls sample size at follow-up	Duration of follow-up	Neuropsychological tests	Rate of decline in MS sample	Impaired cognitive domains
Amato et al. [16]	56	—	2 years	SRT, SRT-D, SPART, SPART-D, SDMT, TMT-A, TMT-B, Tower of London Test, Semantic and Phonemic Verbal Fluency Test, Oral Denomination Test from the Aachener Aphasia Test	70% (failure on at least 3 tests) (change in CCI between baseline and 2 years) Deteriorating: 75% Stable: 11.5% Improving: 13.5%	Verbal memory, complex attention, verbal fluency, receptive language
Amato et al. [17]	48	—	5 years	SRT, SRT-D, SPART, SPART-D, SDMT, TMT-A, TMT-B, Tower of London Test, Semantic and Phonemic Verbal Fluency Test, Oral Denomination Test from the Aachener Aphasia Test	38% (failure on at least 3 tests) (change in CCI between baseline and 5 years) Deteriorating: 56% Stable: 18.8% Improving: 25% (change in CCI between years 2 and 5) Deteriorating: 22.9% Stable: 10.4% Improving: 66.7%	Visual–spatial learning, expressive language
MacAllister et al. [18]	12	—	21.58 ± 9.3 months	TMT, COWAT, Boston Naming Test, CELF 3rd edition, WRAML, WMI	5/12 (cognitive decline assessed using the criteria of more tests showing impaired at the time of the 2nd test than at the baseline) 7/12 (cognitive decline assessed using the criteria of decline in z-score composite from the baseline to the time of the 2nd test)	Attention, executive functions, memory
Charvet et al. [19]	62 (MS) 5 (CIS)	—	1.64 ± 0.63 years	WASI, WASI-II, CVLT-C, CVLT-II, EOWPVT, WIAT-II, VMI, Digit Span subtest from WISC-IV, WAIS-IV, TMT	Rate of impairment was 37% at baseline and 33% at follow-up Most participants showed no change while n = 4 (6%) declined on two or more tasks and n = 6 (9%) improved on 2 or more tasks	Visuomotor integration, information processing speed, attention
Hosseini et al. [20]	35	—	Neuropsychological evaluations were conducted at baseline and up to four more assessments, with each evaluation separated by a minimum of 1 year.	SDMT, TMT, WASI, WISC-III	This study examined changes in cognitive maturation in a cohort of pediatric-onset MS patients as a function of age at disease onset and cognitive reserve factors (baseline IQ and parental social status) Younger age at disease onset was associated with a greater likelihood of cognitive decline on both the TMT-B (p = 0.001) and SDMT (p = 0.005)	Younger age at disease-onset increases the vulnerability for disrupted performance on measures of information processing, visual scanning, perceptual/motor speed, and working memory
Till et al. [21]	28	26	13–16 months (mean: 15 months)	WASI, Visual Matching from the WJ Tests of Cognitive Abilities, TMT A-B, SDMT, Conner's Continuous Performance Test (5th edition)–number of omission errors, Vocabulary and Similarities subtests of the WASI, WJ Tests of Achievement, Verbal Fluency Test from DKEFS, VMI, Block Design and Matrix Reasoning subtests from the WASI, TOMAL-2, WSR, Grooved Pegboard test	Improving: 18% in MS group, 86% in control group The RCI method results showed that the majority of patients remained stable or improved over time (21 of 28; 75%), with only seven of 28 patients (25%) demonstrating decline on three or more of the neuropsychological tests. Only 1 of 26 controls (3.8%) showed cognitive deterioration (p < 0.05).	Attention, information processing speed, visuomotor integration, verbal fluency, visual memory, calculation, spelling ability

CCI: cognitive change index; CVLT: California Verbal Learning Test; DKEFS: Delis–Kaplan executive function system; EOWPVT: Expressive One-Word Picture Vocabulary Test; RCI: reliable change index; TOMAL-2: test of memory and learning-2nd edition; WAIS-IV: Wechsler adult intelligence scale 4th edition; WIAT-II: Wechsler Individual Achievement Test-2nd edition.